Requirement of the prolyl isomerase Pin1 for the replication checkpoint

The peptidyl-prolyl isomerase Pin1 has been implicated in regulating cell c ycle progression. Pin1 was found to be required for the DNA replication che ckpoint in Xenopus laevis, Egg extracts depleted of Pin1 inappropriately tr ansited from the G(2) to the M phase of the cell cycle in the presence of t he DNA replication inhibitor aphidicolin. This defect in replication checkp oint function was reversed after the addition of recombinant wild-type Pin1 , but not an isomerase-inactive mutant, to the depleted extract. Premature mitotic entry in the absence of Pin1 was accompanied by hyperphosphorylatio n of Cdc25, activation of Cdc2/cyclin B, and generation of epitopes recogni zed by the mitotic phosphoprotein antibody, MPM-2. Therefore, Pin1 appears to be required for the checkpoint delaying the onset of mitosis in response to incomplete replication.